Variant-specific disruption to Notch signaling in PAX6 microphthalmia and aniridia patient-derived hiPSC optic vesicles

The homeobox-containing transcription factor PAX6 is a key regulator of eye development. Pathogenic heterozygous PAX6 variants lead to variable ocular phenotypes. Missense variants are often associated with milder ocular conditions, although variants in the DNA-binding paired domain which alter target binding lead to severe ocular phenotypes including bilateral microphthalmia, similar to SOX2 anophthalmia syndrome. However, the variant-specific pathway disruption resulting in phenotypic heterogeneity is not well understood. Gene expression analysis (RNA-seq) was carried out on Aniridia (PX and AN) and wildtype control iPSC derived 3D retinal organoids at timepoints day 0, 20 and 35, two clonal lines per condition, three/four replicates per clone.